Multiple studies have been conducted with reverse sequences of D amino acid peptides, sometimes referred to as retro-inversal (also known as retro-inverso, retro-enantio, retro-all) D amino acid peptides, with varying results.
For example, a reverse L amino acid and a retro-inversal D amino acid peptide having similar activity to its native forward L amino acid or D amino acid peptide are disclosed by Guo et al. (J. Pept. Res. 1997 50(3):210-221 and J. Immunol 2002 169:2180-2188) and Shafiee et al. (Invest. Ophthalmol. Vis. Sci. 2000 41: 2378-2388). Specifically, Guo et al. (J. Pept. Res. 1997 50:210-221) showed that a retro-inverso peptide had similar anti-tumor activity to the native forward peptide. Shafiee et al. (Invest. Ophthalmol. Vis. Sci. 2000, 41: 2378-2388) showed that certain D amino acid peptides were approximately two times more potent than their corresponding forward L amino acid peptides at inhibiting retinal angiogenesis in a retinal explant assay.
However, reverse peptides do not always exhibit similar efficacy to their corresponding forward peptide. Nor do they necessarily bind to the same catalytic or receptor site within or on an enzyme or protein as their corresponding forward peptide. For example, Zhou et al. (JBC 2002 277:17476-17485) showed that a retro-inversal D amino acid peptide, which corresponds to a protein located on the HIV virus, binds to the CXCR4 chemokine receptor, but acts as an antagonist to the natural HIV protein ligand. Buchet et al. (Biochem. Biophys. Acta 1996 1315:40-46) showed that the retro-inversal peptide of Aβ[35-25] altered the aggregation properties of the natural Aβ[25-35] peptide (i.e. random coil structure vs. β-sheet structure). Hwang et al. (Biochem. J. 2006 395:165-172) showed that the reverse L amino acid peptide of NSA9, a peptide derived from human prothrombin kringle-2, and NSA7, a truncated form of NSA9, did not have the same anti-proliferative effects as the natural L amino acid peptides.